阿霉素与胃癌单克隆抗体交联物的体内外抗肿瘤作用

以氧化葡聚糖法制备了阿霉素(ADM)与胃癌单克隆抗体(MoAb)3H11的交联物3H11-DEX-ADM,ADM与3H11克分子比为73:1。经ELISA法测定,交联物的抗体活性保留86%。体外细胞毒试验显示,3H11-DEX-ADM对胃癌细胞BGC823的杀伤作用比游离ADM明显增强,其IC₅₀分别为1.0μg/ml及3.75μg/ml。在荷瘤裸鼠治疗实验中3H11-DEX-ADM能显著抑制肿瘤生长,抑制率为51.5%(P<0.05),明显高于ADM组及其非特异性抗体交联物(NI gG-DEX-ADM)组,后者的抑制率分别为21%及24%。表明3H11-DEX-ADM对肿瘤具有选择杀伤作用。将3H11-DEX-ADM与丝裂霉素C(MMC)-3H11交联物(3H11-HSA-MMC)联合应用,细胞素实验未能显示协同或相加作用;游离ADM与MMC联合亦呈相似结果。

THE ANTITUMOR DFFECT OF ADRIAMYCIN CONJUGATED WITH MONOCLONAL ANTIBODY AGAINST GASTRIC CANCER IN VITRO AND IN VIVO

Adriamycin (ADM), an anthracycline cytotoxic agent, was conjugated with monoclonal antibody 3H11 against gastric cancer via the dextran bridge method. The conjugate 3H11-DEX-ADM, with molar ratio of 3H11 to ADM being 1:73, retained antibody activity to 86%. In the cytotoxicity assay, 3H11-DEX-ADM was shown to exhibit increased cytotoxicity against the target cell line BGC 823. Its IC50 was 3.75 fold less than that of free ADM. The antitumor effect of the conjugate was evaluated in tumor-bearing nude mice. The results indicate that the specific antibody conjugate 3H11-DEX-ADM can significantly inhibit the tumor growth. At the dosage level used in the present study (5 micrograms/mouse x 6), 3H11-DEX-ADM showed an inhibition rate of 51.5%, whereas only moderate inhibition rates were observed with free ADM and the control conjugate NIgG-DEX-ADM. In addition, experiment was performed to evaluate the combined cytotoxicity of 3H11-DEX-ADM and the conjugate of mitomycin C (3H11-HSA-MMC) at different ratios. It was shown that the combination has no synergistic effect when their IC50 was compared with that of the two conjugates used alone. The same result was observed on combinations of the two corresponding free drugs.